Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• , compound 7 has a primary alkyl group (n-propyl). This difference reduces steric hindrance and lowers the rotational barrier around the carbon–nitrogen bond, increasing the likelihood of racemization. Results and Discussion N-Propyl-N-cinnamoylamide 7 was prepared from phosphine oxide 8 [32] via an SNAr

• detector and found that the C(aryl)–N(amide) bond axial chirality exists in amide compound 7. We attempted the optical resolution of racemic compound (±)-7 and obtained (+)-7 and (−)-7 using a semi-preparative chiral HPLC on 50 milligram scales. We also investigated the racemization process associated with

• the axial chirality of compound 7 (see Supporting Information File 1). The racemization barrier (ΔG‡rac) of (−)-7 in n-dodecane was determined to be 25.0 kcal/mol at 25 °C, as calculated using the Arrhenius and Eyring equations [33][34][35]. Therefore, the half-life of racemization of ligand (−)-7 at

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• mixture of right- and left-handed propellers can be resolved by chiral high pressure liquid chromatography (HPLC) into the P- and M-enantiomers, respectively [40][41]. However, due to the low racemization barrier of only about 22 kcal mol−1, the enantiomers racemize within minutes at room temperature. TTM

• is synthesized with slightly improved ϕ of 2% and a blue-shifted emission compared to PTM with a maximum photoluminescence wavelength λem = 569 nm (in CCl4) [40][42]. The racemization barrier remains almost identical at 21.1 kcal mol−1. Both PTM and TTM exhibit circularly polarized emission (CPL) for

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• moiety are non-linear with a Ca–N–C angle of 100°. Due to the stereospecificity of the reaction, racemization would have to occur already in 9 through a topomerization (e.g., similar to a Berry pseudorotation) of the metal complex, considering that species with a quaternary carbon, as they appear in

• experimentally achievable ee values. Maximal theoretical ee values are 70% "S" for Z-hydrazone and 70% "R" for E-hydrazone. The relatively high racemization barriers in 9 preclude a Curtin–Hammett scenario (with fast pre-equilibrium), which would otherwise render the enantiomeric outcome (ee value) independent

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• generation of chiral secondary alkylcopper species has been a significant challenge in organic synthesis, primarily due to their inherent instability and tendency to racemization [38]. For generating the key chiral organocopper intermediates, two distinct approaches have been developed: one utilizing chiral

• the Li/I exchange is essential for preventing racemization of the configurationally labile organolithium intermediate. The subsequent transmetalation with CuBr·P(OEt)3 introduces P(OEt)3 as a supporting ligand, which plays a vital role in stabilizing the resulting chiral organocopper species 14. A key

• importance of reaction conditions after ZnCl2 addition (Scheme 5). When the reaction mixture was stirred at −30 °C for 1 hour (entry 1 in Scheme 5), the product 19 maintained a high diastereomeric ratio (dr), indicating minimal racemization. However, extending the stirring time or increasing the reaction

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• racemization when treated with inorganic bases [25], which had led us to check the equilibrium between Michael and the retro-Michael reaction (Scheme 1). These observations have prompted us to conduct further research into this reaction for potential applications in the kinetic resolution of these adducts. In

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• enantioselectivities were achieved. The products showed no thermal racemization at 150 °C, what was supported by a calculated high rotational barrier of 49.9 kcal/mol. The usefulness of chiral phosphoric acids also shows in the atroposelective Pictet–Spengler reaction of N-arylindoles 104 with various aldehydes 105

• enantioselectivities, the authors also calculated the racemization barrier of products 133. It was determined as a class-3 atropoisomer with 30.1 kcal/mol at 90 °C in toluene. The preparation of 133 on a gram scale yielded 75% of the product with a similar level of enantiomeric purity (90% ee). A key step of this

• stereoselectivity (96% ee, >95:5 dr). No racemization was observed after 36 hours at 150 °C in o-xylene. The asymmetric synthesis of arylindolylindolinones 139 or 141 bearing both central and axial chirality was accomplished by a combination of arylindoles 137 or 140 and indolinones 138 with CPA (R)-C22 acting as

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• structure of verrulactone A was later unambiguously confirmed by X-ray crystallographic analysis [160]. Chirality and absolute configurations remained unresolved, where it should be noted that even verrulactones A and B are axially chiral with an assumed significant racemization barrier. At least it has

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• compounds 4a–j were also obtained in very good yields (60–98%, Scheme 2). Since the reaction mechanism proceeding with a Wagner–Meerwein rearrangement does not cause racemization or a diastereomeric mixture and preserves the initial enantiomeric excess in the camphene's fluoroalkoxy derivatives (Scheme 4

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• 50 mmol scale [60]. Little racemization (<7%) of 77 occurred during the reaction. The simplicity of the Kropp protocol resulted in a report in the journal of chemical education [61]. Similar work was reported by Delaude and co-workers [62]. They studied a series of zeolites for the hydrochlorination

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• isomerization and photochemical (only for 13a) isomerization [46]. Compounds 13 showed intrinsic planar chirality and their enantiomers could be separated by HPLC. Notably, upon thermal and photochemical isomerization of these compounds, no Z-isomers were detected and only the racemization took place. Such

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• in the visible region were evident in their CD spectra. Using the Arrhenius and Eyring formalisms, the kinetic parameters for the thermal racemization of 57 and 58 were obtained. The activation free enthalpy (ΔG‡) for the racemization of 57 (ΔG‡298 K = 24.8 kcal mol−1) was ≈1.5 kcal mol−1 larger than

• determined the absolute configurations of these atropisomers through the X-ray crystallographic analyses of (Sa)-59 and (Ra)-60. Surprisingly, heating the enantiomers of 69 and 60 at 80 °C for 3 h resulted in negligible thermally induced racemization. Meanwhile, in O2-free toluene solution under illumination

• , the racemization was observed at 80 °C. Torres et al. performed detailed theoretical calculations and showed that the racemization observed in 59 and 60 is caused by triplet-state photogeneration, which leads to the rotation around the sterically hindered buta-1,3-diene chiral axis [132]. In fact, the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• has been used to cure a liquid isoprene polymer in precise digital light processing 3D printing [105]. Recently, Kanbayashi et al. reported that thiol–ene chemistry would not cause racemization of an asymmetric center linked to a pendant vinyl group, which can be particularly valuable for

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• reacted immediately (one-pot procedure) with sodium borohydride to give 4.4. It must be noted that this sequence does not induce racemization and that 4.4 can be stored for months with 0.5% of solid KOH acting as a stabilizer [72]. Then, 4.4 was alkylated with stearyl tosylate to produce 4.5. The two

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• chiral nanographenes. Keywords: chiral nanographene; helicene; racemization barrier; Scholl reaction; single-crystal X-ray diffractometry; Introduction Graphene, an allotrope of carbon, has captured widespread attention since it was first experimentally demonstrated as a monolayer of carbon atoms [1

• determined for the enantiopure helicenes. For compound 12, the racemization barrier was 24.8 kcal mol−1 at 298 K, which provides a racemization half-life (t1/2) of 24.4 h. For compounds 11 and 13, neither racemization nor decomposition was observed by chiral HPLC after heating hexadecane solutions of each

• compound at 200 °C for 5 h, which gives a lower limit to the barrier of racemization of ΔG > 38.3 kcal mol−1 at 473 K. The circularly polarized luminescence (CPL) of these structures were also evaluated with the luminescence dissymmetry factors (glum) values of 4 × 10−4 for compound 11 and 7 × 10−4 for

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• chirality which exhibits no racemization under action of strong bases [29]. The chiral N–H-containing rimantadine-based ligand (L6) is highly lipophilic and it was successfully used for the kinetic resolution of unprotected racemic amino acids [30]. The examples mentioned above show that the metal–Schiff

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• rotation of the isolated products 43a–h did not show any racemization under the standard reaction conditions. Thereafter, imidazolium salts 45a–d, obtained from imidazole N-oxides 44a–d, provided the desired optically active 3-butoxyimidazole-2-thiones 47a–d in 66–83% yield using triethylamine in pyridine

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• . Ultimately, enantiomeric purities of >99% ee were reached for both 6a and 6b (Figure S4, Supporting Information File 1). The compounds were subsequently converted into the diphosphates. To exclude partial racemization during this conversion, small samples of each enantiomer of 2-Me-LPP were dephosphorylated

• available, and their conversion into the enantiomers of 2-Me-LPP proceeds without noticeable racemization, leading to materials of >99% ee. Incubation of both pure enantiomers revealed that (R)-2-Me-LPP is the on-pathway intermediate towards 1, while its formation from (S)-2-Me-LPP may be explained through

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• yield when HATU/DIPEA as the coupling reagent was used (Table 1, entry 2). Only trace product could be detected with EEDQ (Table 1, entry 4). Further screening did not give better results (Table 1, entries 5 and 6). The purity of tripeptide 7 was determined by HPLC and no racemization was observed

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• good yields (24 to >99%) with poor to moderate ee (9 to 55%). A complete reversal of stereoselectivity was observed on introducing a benzoyl group in cinchonine and cinchonidine. It was demonstrated that racemization occurred in suitable solvents under mild conditions due to retro-MR of the initially

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• enantioselective synthetic strategies towards 2,3-dihydroquinazolinone derivatives has drawn the attention of organic chemists for a long time [14][15][16][17][18], even though the aminal stereocenter is sensitive to racemization [12]. The well-established and straightforward approach in the asymmetric

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• alkynylations of bioactive structural motifs are rare [63]. In 2017, the Ackermann group disclosed a late-stage Mn(I)-catalyzed C–H alkynylation of various complex peptide scaffolds [64]. As shown in Scheme 9, manganese(I) catalysis remarkably resulted in racemization-free alkynylation, representing a step

• ]. Based on an initial optimization study, manganese(I) pentacarbonyl bromide was deemed as the optimal catalyst, enabling a robust racemization-free allylation process. In addition to tryptophan-containing peptides, diazepam and nucleoside analogues were found to be viable allylation substrates, affording

• , a natural product scaffold, was transformed into glycosylated tryptophan 31f. It is noteworthy that this manganese(I)-catalyzed glycoconjugation method avoids racemization. Furthermore, manganese-catalyzed allylative linchpin C–H glycosylation was investigated using structurally sophisticated

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• major drawbacks identified with the Prins cyclization are the racemization due to competing oxonia-Cope rearrangement and side-chain exchange. Willis and co-workers studied the reactivity of the Prins reaction of different aryl group-substituted homoallylic alcohols 18 with propanal in the presence of a

• % yield and <5% ee. The poor enantiomeric excess of the product 23 indicates that the racemization takes place during the course of the reaction. It was explained that the reason for the loss of optical purity was due to the formation of a benzylic cation, which is stabilized by the electron-rich aromatic

• propanal, which proceeded with high selectivity to give the corresponding THP 28 (79% ee, 32% yield) along with some recovered starting material (47%), as shown in Scheme 6. Partial racemization was also reported at the same time by reversible 2-oxonia-Cope rearrangement and via side-chain exchange [31][32

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• , indicating a racemization during the reaction process. The less polar isomer with R-configuration [31][32] at C2 showed a complete loss of β-lactamase inhibition activity as compared to the more polar isomer. Therefore, the less polar isomer was discarded while saving the more polar S-isomer, (relative ratio

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• followed by oxidation. The corresponding phosphinyl depsipeptides 107 were generated and further oxidized into phosphonyl depsipeptides 108 (Scheme 17) [32]. The protected phosphonodepsidipeptides 111 were prepared without racemization from N-Cbz-protected α-aminoalkylphosphonic monomethyl (12h) or benzyl

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• occurred with 41% inversion (and 59% racemization, i.e., product 23f was obtained with an enantiomeric ratio of ca. 70:30 in favor of the (S)-enantiomer), while complete racemization was observed in more ionizing TFA or HFIP as the solvent (Figure 5b) [48]. These observations are in agreement with a